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1.
J Am Chem Soc ; 146(2): 1435-1446, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38174986

RESUMO

Most currently known n-type conjugated polymers have a semiflexible chain topology, and their charge carrier mobilities are known to peak at modest chain lengths of below 40-60 repeat units. Herein, we show that the field-effect electron mobility of a model n-type conjugated polymer that has a rigid-rod chain topology grows continuously without saturation, even at a chain length exceeding 250 repeat units. We found the mechanism underlying the novel chain length-dependent electron transport to originate from the reduced structural disorder and energetic disorder with the increasing degree of polymerization inherent to the rigid-rod chain topology. Furthermore, we demonstrate a unique chain length-dependent decay of threshold voltage, which is rationalized by decreased trap densities and trap depths with respect to the degree of polymerization. Our findings provide new insights into the role of polymer chain topology in electron transport and demonstrate the promise of rigid-rod chain architectures for the design of future high-mobility conjugated polymers.

2.
Chem Rev ; 122(24): 17397-17478, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36260695

RESUMO

Hierarchical materials that exhibit order over multiple length scales are ubiquitous in nature. Because hierarchy gives rise to unique properties and functions, many have sought inspiration from nature when designing and fabricating hierarchical matter. More and more, however, nature's own high-information content building blocks, proteins, peptides, and peptidomimetics, are being coopted to build hierarchy because the information that determines structure, function, and interfacial interactions can be readily encoded in these versatile macromolecules. Here, we take stock of recent progress in the rational design and characterization of hierarchical materials produced from high-information content blocks with a focus on stimuli-responsive and "smart" architectures. We also review advances in the use of computational simulations and data-driven predictions to shed light on how the side chain chemistry and conformational flexibility of macromolecular blocks drive the emergence of order and the acquisition of hierarchy and also on how ionic, solvent, and surface effects influence the outcomes of assembly. Continued progress in the above areas will ultimately usher in an era where an understanding of designed interactions, surface effects, and solution conditions can be harnessed to achieve predictive materials synthesis across scale and drive emergent phenomena in the self-assembly and reconfiguration of high-information content building blocks.


Assuntos
Peptídeos , Substâncias Macromoleculares/química
3.
Acta Neurochir (Wien) ; 166(1): 113, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416213

RESUMO

INTRODUCTION: Spheno-orbital meningiomas (SOMs) represent a distinct subtype of meningioma characterized by their unique multi-compartmental invasion pattern. Previous studies have investigated correlations between SOMs and visual manifestations. However, our comprehension of pain associated with SOMs remains limited. This study aims to provide insight into the pathophysiology underlying SOM-related pain through measurements of tumor volume and superior orbital fissure (SOF) narrowing. METHODS: This retrospective study included patients who underwent surgical resection of a SOM between 2000 and 2022. Preoperative CT and/or MRI scans were analyzed, and the tumor volume of each segment was measured. Bony 3D reconstructions were used to measure the area of the SOF, and SOF narrowing was calculated. RESULTS: The study cohort included 66 patients diagnosed with SOMs, among which 25.8% (n = 17) presented with pain. Postoperatively, 14/17 (82.4%) of patients reported pain improvement. There was no significant correlation between the total volume or the volume of tumor within each compartment and the presence of pain on presentation (p > 0.05). The median SOF narrowing was significantly different between patients presenting with and without tumor-associated pain with median of 11 mm2 (IQR 2.8-22.3) and 2 mm2 (IQR 0-6), respectively (p = 0.005). Using logistic regression, a significant correlation between the degree of SOF narrowing and the presence of SOM-associated pain on presentation was identified, with an aOR of 1.2 (95% CI 1.12-1.3, p = 0.02). CONCLUSION: While the exact cause of tumor-associated pain remains unclear, SOF narrowing seems to play a role in pain among SOM patients. Based on the radiological characteristics, SOF neurovascular decompression is recommended in SOM patients.


Assuntos
Dor do Câncer , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Estudos Retrospectivos , Dor , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia
4.
J Am Chem Soc ; 145(3): 1866-1876, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36630664

RESUMO

We study the organic electrochemical transistor (OECT) performance of the ladder polymer poly(benzimidazobenzophenanthroline) (BBL) in an attempt to better understand how an apparently hydrophobic side-chain-free polymer is able to operate as an OECT with favorable redox kinetics in an aqueous environment. We examine two BBLs of different molecular masses from different sources. Regardless of molecular mass, both BBLs show significant film swelling during the initial reduction step. By combining electrochemical quartz crystal microbalance gravimetry, in-operando atomic force microscopy, and both ex-situ and in-operando grazing incidence wide-angle X-ray scattering (GIWAXS), we provide a detailed structural picture of the electrochemical charge injection process in BBL in the absence of any hydrophilic side-chains. Compared with ex-situ measurements, in-operando GIWAXS shows both more swelling upon electrochemical doping than has previously been recognized and less contraction upon dedoping. The data show that BBL films undergo an irreversible hydration driven by the initial electrochemical doping cycle with significant water retention and lamellar expansion that persists across subsequent oxidation/reduction cycles. This swelling creates a hydrophilic environment that facilitates the subsequent fast hydrated ion transport in the absence of the hydrophilic side-chains used in many other polymer systems. Due to its rigid ladder backbone and absence of hydrophilic side-chains, the primary BBL water uptake does not significantly degrade the crystalline order, and the original dehydrated, unswelled state can be recovered after drying. The combination of doping induced hydrophilicity and robust crystalline order leads to efficient ionic transport and good stability.

5.
Compr Rev Food Sci Food Saf ; 22(3): 2292-2309, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37010110

RESUMO

Bread dough and bread are dispersed systems consisting of starch polymers that interact with other flour components and added ingredients during processing. In addition to gluten proteins, starch impacts the quality characteristics of the final baked product. Wheat starch consists of amylose and amylopectin organized into alternating semicrystalline and amorphous layers in granules that vary in size and are embedded in the endosperm protein matrix. Investigation of the molecular movement of protons in the dough system provides a comprehensive insight into granular swelling and amylose leaching. Starch interacts with water, proteins, amylase, lipids, yeast, and salt during various stages of breadmaking. As a result, the starch polymers within the produced crumb and crust, together with the rate of retrogradation and staling due to structural reorganization, moisture migration, storage temperature, and relative humidity determines the final product's textural perception. This review aims to provide insight into wheat starch composition and functionality and critically review recently published research results with reference to starch structure-function relationship and factors affecting it during dough formation, fermentation, baking, cooling, and storage of bread.


Assuntos
Amilose , Amido , Amido/química , Amilose/química , Triticum/química , Amilopectina/química , Relação Estrutura-Atividade
6.
AAPS PharmSciTech ; 24(5): 123, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37226039

RESUMO

Solid lipid nanoparticles (SLNs) are used extensively to achieve site-specific drug delivery with improved bioavailability and reduced toxicity. This work focused on a new approach to provide site-specific stimuli-responsive delivery of SLNs loaded within thermo-sonic nano-organogel (TNO) variants to deliver the model chemotherapeutic agent 5-FU in treating cervical cancer. Pharmaceutically stable nanospherical SLNs comprising poly-L-lactic acid (PLA), palmitic acid (PA), and polyvinyl alcohol (PVA) were prepared and incorporated into TNO variants augmented by external thermal and ultrasound stimuli for release of 5-FU in the cervix. Results revealed that rate-modulated 5-FU release was achieved from SLNs (particle size =450.9 nm; PDI =0.541; zeta potential =-23.2 mV; %DL =33%) within an organogel upon exposure to either a single (thermo-) and/or both (thermo-sonic) stimuli. 5FU was released from all TNO variants with an initial burst on day 1 followed by sustained release over 14 days. TNO 1 provided desirable release over 15 days (44.29% vs. 67.13% under single (T) or combined (TU) stimuli, respectively). Release rates were primarily influenced by the SLN:TO ratio in tandem with biodegradation and hydrodynamic influx. Biodegradation by day 7 revealed that variant TNO 1 (1:5) released 5FU (46.8%) analogous to its initial mass than the other TNO variants (i.e., ratios of 2:5 and 3:5). FT-IR spectra revealed assimilation of the system components and corroborative with the DSC and XRD analysis (i.e., in ratios of PA:PLA 1:1 and 2:1). In conclusion, the TNO variants produced may be used as a potential stimuli-responsive platform for the site-specific delivery of chemotherapeutic agents such as 5-FU to treat cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Espectroscopia de Infravermelho com Transformada de Fourier , Fluoruracila , Poliésteres
7.
Actas Esp Psiquiatr ; 51(2): 56-64, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37218100

RESUMO

The lockdown during the first wave of COV- ID-19 in Spain has been related to higher levels of anxiety in the general population. However, the emotional impact on Spanish caregivers of individuals with neurodevelopmental disorders (NDD) has not been studied so far.


Assuntos
Transtorno do Espectro Autista , COVID-19 , Síndrome de Down , Síndrome de Williams , Humanos , Síndrome de Williams/psicologia , Transtorno do Espectro Autista/psicologia , Cuidadores/psicologia , COVID-19/psicologia , Espanha/epidemiologia , Controle de Doenças Transmissíveis , Ansiedade/epidemiologia
8.
Bioorg Med Chem ; 58: 116652, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35180594

RESUMO

The toxicity of existing anticancer agents on healthy cells and the emergence of multidrug-resistance cancer cells have led to the search for less toxic anticancer agents with different mechanisms of action. In this study, a novel class of ferrocenylbisphosphonate hybrid compounds (H1-H8) were designed and characterized using NMR, IR and HRMS. The in vitro anticancer activity of the hybrid compounds on HeLa (cervix adenocarcinoma) and A549 (non-small cell lung cancer cell lines) was evaluated. The structure-activity relationship of the hybrid molecules was also studied. The lead compound, tetraethyl (3-(4-oxo-4-ferrocenylbutanamido) propane-1-1-diylbis(phosphonate) (H6) exhibited higher cytotoxicity on A549 (IC50 = 28.15 µM) than cisplatin (IC50 = 58.28 µM), while its activity on HeLa cells (IC50 = 14.69 µM) was equivalent to that of cisplatin 15.10 µM (HeLa cells). H6 (IC50 = 95.58 µM) was also five times less toxic than cisplatin (IC50 = 20.86 µM) on fibroblast NIH3T3 suggesting that H6 can be a future replacement for cisplatin due to its non-toxicity to healthy cells. Interestingly, some ferrocene and bisphosphonate parent compounds exhibited promising anticancer activity with 4-ferrocenyl-4-oxobutanoic acid (FI) exhibiting higher cytotoxic activity (IC50 = 1.73 µM) than paclitaxel (IC50 = 3.5 µM) on A549 cell lines. F1 also exhibited lower cytotoxicity than paclitaxel and cisplatin on the normal murine fibroblast cell line (NIH3T3). The molecular docking studies showed H6 strong binding affinity for the STAT3 signaling pathway in A549 cell line, and the MAdCAM-1 and cellular tumor antigen p53 proteins in HeLa cell lines.


Assuntos
Antineoplásicos/farmacologia , Difosfonatos/farmacologia , Compostos Ferrosos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Difosfonatos/síntese química , Difosfonatos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Ferrosos/síntese química , Compostos Ferrosos/química , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
9.
Macromol Rapid Commun ; 43(4): e2100639, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35038198

RESUMO

It is reported herein the synthesis of a novel amphiphilic diblock peptoid bearing a terminal conjugated oligoaniline and its self-assembly into small-diameter (D ≈ 35 nm) crystalline nanotubes with high aspect ratios (>30). It is shown that both tetraaniline (TANI)-peptoid and bianiline (BANI)-peptoid triblock molecules self-assemble in solution to form rugged highly crystalline nanotubes that are very stable to protonic acid doping and de-doping processes. The similarity of the crystalline tubular structure of the nanotube assemblies revealed by electron microscopy imaging, and X-ray diffraction analysis of the nanotube assemblies of TANI-functionalized peptoids and nonfunctionalized peptoids showed that the peptoid is an efficient ordered structure directing motif for conjugated oligomers. Films of doped TANI-peptoid nanotubes has a dc conductivity of ca. 95 mS cm-1 , while the thin films of doped un-assembled TANI-peptoids show a factor of 5.6 lower conductivity, demonstrating impact of the favorable crystalline ordering of the assemblies on electrical transport. These results demonstrate that peptoid-directed supramolecular assembly of tethered π-conjugated oligo(aniline) exemplify a novel general strategy for creating rugged ordered and complex nanostructures that have useful electronic and optoelectronic properties.


Assuntos
Nanoestruturas , Nanotubos , Peptoides , Cristalografia por Raios X , Microscopia Eletrônica , Nanoestruturas/química , Nanotubos/química , Peptoides/química
10.
Molecules ; 27(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364474

RESUMO

A series of new 1,2,4-triazolo-linked bis-indolyl conjugates (15a-r) were prepared by multistep synthesis and evaluated for their cytotoxic activity against various human cancer cell lines. It was observed that they were more susceptible to colon and breast cancer cells. Conjugates 15o (IC50 = 2.04 µM) and 15r (IC50 = 0.85 µM) illustrated promising cytotoxicity compared to 5-fluorouracil (5-FU, IC50 = 5.31 µM) against the HT-29 cell line. Interestingly, 15o and 15r induced cell cycle arrest at the G0/G1 phase and disrupted the mitochondrial membrane potential. Moreover, these conjugates led to apoptosis in HT-29 at 2 µM and 1 µM, respectively, and also enhanced the total ROS production as well as the mitochondrial-generated ROS. Immunofluorescence and Western blot assays revealed that these conjugates reduced the expression levels of the PI3K-P85, ß-catenin, TAB-182, ß-actin, AXIN-2, and NF-κB markers that are involved in the ß-catenin pathway of colorectal cancer. The results of the in silico docking studies of 15r and 15o further support their dual inhibitory behaviour against PI3K and tankyrase. Interestingly, the conjugates have adequate ADME-toxicity parameters based on the calculated results of the molecular dynamic simulations, as we found that these inhibitors (15r) influenced the conformational flexibility of the 4OA7 and 3L54 proteins.


Assuntos
Antineoplásicos , Tanquirases , Humanos , beta Catenina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Antineoplásicos/farmacologia , Apoptose , Fluoruracila/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
11.
Trop Anim Health Prod ; 54(2): 103, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35157179

RESUMO

Equine piroplasmosis (EP) is a tick-borne disease of equines with resultant economic consequences. To date, little information is available regarding the effects of EP on the health of equids in Nigeria. Therefore, this study was carried out to ascertain the effects of natural sub-clinical infection with T. equi on the hematology and biochemical profiles of horses and donkeys. Blood and serum samples were subjected to hematology and serum biochemistry analyses, respectively. Data corresponding to PCR-positive (infected) and PCR-negative (uninfected) was computed to ascertain changes in any of the parameters. Hematological significant findings (P<0.001) in both horses and donkeys include decreased packed cell volume (PCV), red blood cell (RBC) count, hemoglobin (Hb) concentration, and white blood cell (WBC) counts in the infected group compared to the uninfected group. In horses, the PCV (%) and Hb (g/dL) values were 40.6±1.0 and 13.4±1.7 in the uninfected group compared with 30.8±0.6 and 10.1±0.3 in the infected group respectively and differs significantly (P<0.001). Similarly, in the donkeys, the PCV (%) and Hb (g/dL) values were 32.2 ± 0.5 and 10.5 ± 0.2 in the uninfected group compared with 28.5±0.7 and 9.5±0.2 in the infected group respectively with significant difference (P<0.001). Additionally, we observed a slight decrease in WBC counts (×103/µL) in the infected group in horses (9.9±0.4) and donkeys (10.2±4.3) compared with 10.5±2.0 and 13.0±0.8 from the uninfected respectively. Serum biochemical profiles revealed slight increase in the levels of total proteins principally the globulin fractions in the infected group in both equids. The findings from this study will be helpful in the diagnosis, prognosis, and treatment evaluation of equines in Nigeria.


Assuntos
Babesiose , Doenças dos Bovinos , Hematologia , Doenças dos Cavalos , Theileria , Theileriose , Animais , Bovinos , Doenças dos Cavalos/epidemiologia , Cavalos , Nigéria , Theileriose/epidemiologia
12.
Nat Mater ; 19(7): 738-744, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32152564

RESUMO

Doping of organic semiconductors is crucial for the operation of organic (opto)electronic and electrochemical devices. Typically, this is achieved by adding heterogeneous dopant molecules to the polymer bulk, often resulting in poor stability and performance due to dopant sublimation or aggregation. In small-molecule donor-acceptor systems, charge transfer can yield high and stable electrical conductivities, an approach not yet explored in all-conjugated polymer systems. Here, we report ground-state electron transfer in all-polymer donor-acceptor heterojunctions. Combining low-ionization-energy polymers with high-electron-affinity counterparts yields conducting interfaces with resistivity values five to six orders of magnitude lower than the separate single-layer polymers. The large decrease in resistivity originates from two parallel quasi-two-dimensional electron and hole distributions reaching a concentration of ∼1013 cm-2. Furthermore, we transfer the concept to three-dimensional bulk heterojunctions, displaying exceptional thermal stability due to the absence of molecular dopants. Our findings hold promise for electro-active composites of potential use in, for example, thermoelectrics and wearable electronics.

13.
Curr Hypertens Rep ; 23(3): 16, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33694011

RESUMO

PURPOSE OF REVIEW: Cardiovascular diseases (CVD), including pre-eclampsia (PE), remain the major cause of death and morbidity in women. This review elucidates the current knowledge, state of research and scientific information available on the post-event implications and complications of PE regarding maternal and foetal cardiovascular health. Does PE expose, predispose or aggravate a predilection to maternal and foetal CVD later in life? RECENT FINDINGS: Women with a history of PE are reported to have stiffer arteries and are more likely to develop cardiovascular problems with time, especially aortic stenosis and mitral regurgitation, which were not hitherto linked with hypertensive pregnancy. Foetal cells persistence in the mother long after pregnancy, now clearly established in the lungs of mice postpartum, is suggested to portend an overexpression of STOX1, which may potentiate later life CVD. Moreover, the conventional theories of in utero stress and developmental reprogramming may not adequately explain the risk of later life CVD predilection in offspring born to mothers with pre-eclampsia as recent data has shown that siblings of offspring born from pre-eclamptic pregnancies are also at higher risk of hypertension later in life, irrespective of whether subsequent pregnancies were pre-eclamptic or normotensive. The mechanism involved in adverse cardiovascular outcome in offspring of pre-eclamptic pregnancies is most likely an intricate interaction of foetal programming, environmental and genetic factors. In light of available evidence, the question of whether PE is just a pointer or predisposing factor to maternal development of CVDs in later life begs for answers to facilitate definitive clinical solutions and preventive approaches.


Assuntos
Doenças Cardiovasculares , Hipertensão , Pré-Eclâmpsia , Animais , Proteínas de Transporte , Criança , Feminino , Humanos , Camundongos , Mães , Período Pós-Parto , Gravidez
14.
Molecules ; 26(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34684718

RESUMO

The infrared heating of preconditioned cowpea improves its utilization and potential application in food systems. This study investigated the effect of optimizing preconditioning and infrared heating parameters of temperature and time on cooking characteristics of precooked cowpeas using response surface methodology (RSM). The moisture level (32-57%), infrared heating temperature (114-185 °C), and time of processing the seeds (2-18 min) were optimized using a randomized central composite design to achieve optimal characteristics for bulk density and water absorption. A second-order polynomial regression model was fitted to the obtained data, and the fitted model was used to compute the multi-response optimum processing conditions, which were the moisture of 45%, the heating temperature of 185 °C, and time of 5 min. Precooked cowpea seeds from optimized conditions had a 19% increase in pectin solubility. The total phenolic and total flavonoid contents were significantly reduced through complexation of the seeds' phenolic compounds with other macromolecules but nonetheless exhibited antioxidant properties capable of scavenging free radicals. There was also a significant reduction in phytate and oxalates by 24% and 42%, respectively, which was due to the heat causing the inactivation of these antinutrients. The obtained optimized conditions are adequate in the production of precooked cowpea seeds with improved quality.


Assuntos
Culinária/métodos , Calefação/métodos , Vigna/metabolismo , Antioxidantes/análise , Flavonoides/análise , Manipulação de Alimentos/métodos , Temperatura Alta , Raios Infravermelhos , Fenóis/análise , Sementes/química , Solubilidade , Temperatura , Água
15.
J Food Sci Technol ; 57(10): 3688-3695, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32903942

RESUMO

Amadumbe, commonly known as taro is a traditional southern African tuber crop. In this study, the effect of corm size: large, medium and small on composition and functional properties of amadumbe flours and starch isolates was determined. With the exception of iron and zinc, the basic chemical composition of amadumbe flours was not affected by differences in corms size. Amadumbe flours contained substantial amount of carbohydrates and limited contents of protein and fat. However, flours derived from large and small corms had iron contents (approx. 3 mg/100 g), which was 3 times that of medium corms. Large corms flour had the highest Zn content (2.6 mg/100 g). Amadumbe corms showed polygonal and small sized (1-5 µm) starch granules containing varying levels of amylose (13-16%). Starch isolates showed reflective peaks at 15° (2θ) and doublet at 17° and 18° typical of A-type starches. Peak viscosity, gelatinisation temperatures and final peak viscosity significantly varied among amadumbe corm types possibly due to variation in amylose contents. Flour mineral content, starch amylose and functionality differ with corm types.

16.
Chemistry ; 24(37): 9217-9219, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29644772

RESUMO

The principal active component produced by highly attractive senesced host banana leaves, Musa spp., for the banana weevil, Cosmopolites sordidus, is shown by coupled gas chromatography-electroantennography (GC-EAG), coupled GC-mass spectrometry (GC-MS), chemical synthesis and coupled enantioselective (chiral) GC-EAG to be (2R,5S)-theaspirane. In laboratory behaviour tests, the synthetic compound is as attractive as natural host leaf material and presents a new opportunity for pest control.


Assuntos
Musa/química , Norisoprenoides/isolamento & purificação , Feromônios/isolamento & purificação , Folhas de Planta/química , Gorgulhos , Animais , Norisoprenoides/química , Controle de Pragas , Feromônios/química , Estereoisomerismo
17.
Trop Anim Health Prod ; 50(7): 1573-1582, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29680957

RESUMO

Using a cross-sectional survey, we determined the prevalence and risk factors associated with bovine brucellosis in herds under extensive production system in southwestern Nigeria. Antibodies to Brucella species in serum samples were tested using the Rose Bengal test (RBT) and competitive enzyme-linked immunosorbent assay (cELISA); for milk, the milk ring test (MRT) and indirect-ELISA (i-ELISA) were used. Questionnaire was administered to cattle herdsmen to determine factors predisposing the animals to bovine brucellosis. Data were analyzed using STATA 12. From 513 serum and 635 milk samples tested among 120 herds, overall animal-level prevalence of 10.1% (95% CI 7.5-12.7%) and 20.2% (95% CI 17.1-23.3%) were recorded by RBT and MRT, respectively; while 9.4% (95% CI 6.9-11.9%) and 17.8% (95% CI 14.8-20.8%) were obtained using cELISA and i-ELISA, respectively. In all, from the 120 herds tested, 29.2% and 43.3% were positive by RBT and MRT, respectively. Multivariable logistic regression revealed that herd location (OR = 8.12, 95% CI 1.68-38.90) and improper disposal of placenta/fetus (OR = 17.33, 95% CI 4.81-62.33) were predictors for a seropositive herd using RBT; while herd location (OR = 5.13, 95% CI 1.27-20.28), large herd size (OR = 2.62, 95% CI 1.15-5.85), and occurrence of abortion for a year or more (OR = 4.62, 95% CI 1.53-13.71) were predictors of seropositivity to antibodies to Brucella spp. using MRT. We found high prevalence of brucellosis in cattle herds under extensive management system in southwestern Nigeria. Urgent and coordinated control strategies are required to mitigate this problem.


Assuntos
Criação de Animais Domésticos/métodos , Brucelose Bovina/epidemiologia , Bovinos/microbiologia , Animais , Anticorpos , Brucella , Brucelose Bovina/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Modelos Logísticos , Leite , Nigéria/epidemiologia , Gravidez , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Inquéritos e Questionários
18.
J Asthma ; 54(10): 1033-1040, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28332884

RESUMO

OBJECTIVE: The asthma control test (ACT) is a validated tool for assessing control in asthmatic children aged 12 years and older. Using the ACT, we sought to assess asthma control and knowledge in London secondary school children. METHODS: Secondary schools in London, UK, participated in this study. Children with doctor-diagnosed asthma were invited to complete an online questionnaire that included the ACT and questions about asthma. Suboptimal asthma control was defined as an ACT score of ≤ 19 out of a maximum score of 25. Data are summarised as median and interquartile range (IQR), and were analysed by either Mann-Whitney test, or chi-square test. A p value of < 0.05 was considered significant. RESULTS: A total of 799 children completed the questionnaire; 689 (86.2%) were included for analysis. Suboptimal asthma control was reported by 49.6% of students. Over a third (42.4%) of students prescribed a short-acting ß2-agonist inhaler felt uncomfortable using it at school, and 29.2% (n = 173) reported not using this inhaler when wheezy. 56.4% (n = 220) of those with regular inhaled corticosteroids did not take them as prescribed, and 41.7% did not know what this inhaler was for. Suboptimal control was associated with a greater proportion of students reporting that they were 'somewhat', 'hardly' or 'not at all' comfortable using inhalers at school (52.7% vs 29.1%, p < 0.01) and outside school (22.8% vs. 14.8%, p < 0.01). CONCLUSIONS: Suboptimal asthma control and poor asthma knowledge are common in London schoolchildren.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Instituições Acadêmicas , Administração por Inalação , Adolescente , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Criança , Quimioterapia Combinada , Feminino , Humanos , Londres , Masculino , Adesão à Medicação , Qualidade de Vida , Grupos Raciais
19.
J Virol ; 89(23): 12058-69, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26401032

RESUMO

UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) replication requires reverse transcription of its RNA genome into a double-stranded cDNA copy, which is then integrated into the host cell chromosome. The essential steps of reverse transcription and integration are catalyzed by the viral enzymes reverse transcriptase (RT) and integrase (IN), respectively. In vitro, HIV-1 RT can bind with IN, and the C-terminal domain (CTD) of IN is necessary and sufficient for this binding. To better define the RT-IN interaction, we performed nuclear magnetic resonance (NMR) spectroscopy experiments to map a binding surface on the IN CTD in the presence of RT prebound to a duplex DNA construct that mimics the primer-binding site in the HIV-1 genome. To determine the biological significance of the RT-IN interaction during viral replication, we used the NMR chemical shift mapping information as a guide to introduce single amino acid substitutions of nine different residues on the putative RT-binding surface in the IN CTD. We found that six viral clones bearing such IN substitutions (R231E, W243E, G247E, A248E, V250E, and I251E) were noninfectious. Further analyses of the replication-defective IN mutants indicated that the block in replication took place specifically during early reverse transcription. The recombinant INs purified from these mutants, though retaining enzymatic activities, had diminished ability to bind RT in a cosedimentation assay. The results indicate that the RT-IN interaction is functionally relevant during the reverse transcription step of the HIV-1 life cycle. IMPORTANCE: To establish a productive infection, human immunodeficiency virus type 1 (HIV-1) needs to reverse transcribe its RNA genome to create a double-stranded DNA copy and then integrate this viral DNA genome into the chromosome of the host cell. These two essential steps are catalyzed by the HIV-1 enzymes reverse transcriptase (RT) and integrase (IN), respectively. We have shown previously that IN physically interacts with RT, but the importance of this interaction during HIV-1 replication has not been fully characterized. In this study, we have established the biological significance of the HIV-1 RT-IN interaction during the viral life cycle by demonstrating that altering the RT-binding surface on IN disrupts both reverse transcription and viral replication. These findings contribute to our understanding of the RT-IN binding mechanism, as well as indicate that the RT-IN interaction can be exploited as a new antiviral drug target.


Assuntos
Integrase de HIV/metabolismo , Transcriptase Reversa do HIV/metabolismo , HIV-1/fisiologia , Transcrição Reversa/fisiologia , Replicação Viral/fisiologia , Substituição de Aminoácidos/genética , Western Blotting , Primers do DNA/genética , Escherichia coli , Integrase de HIV/genética , Transcriptase Reversa do HIV/genética , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Reação em Cadeia da Polimerase em Tempo Real
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